Nano- and Microstructured Biomaterials for Spinal Cord Injury Repair: From Material Design to Neural Regeneration.

Spinal cord injury (SCI) is one of the most devastating neurological disorders, frequently resulting in severe functional deficits and paralysis. However, effective repair remains a major clinical challenge due to the complex pathological cascade following injury and the limited regenerative capacity of the central nervous system. Over the past decades, biomaterials have emerged as promising platforms for promoting SCI repair. By providing biochemical, biophysical, and topographical cues across nano-, micro-, to mesoscales, biomaterials can modulate key molecular and cellular processes during SCI progression, including the enhancement of neurotrophic support, neutralization of inhibitory factors, and regulation of specific spinal cell populations, thereby alleviating intrinsic and extrinsic insults while facilitating neural regeneration and circuit reconnection. Within this context, the review first dissects the pathological barriers that impede neural regeneration after SCI. We then provide an overview of recent advancements in nanomaterials, microstructured scaffolds, and hierarchical systems, with a focus on their design principles and functional roles in remodeling the injury microenvironment, delivering therapeutic signals, and providing structural support and guidance for tissue regeneration. Furthermore, biomaterial-based clinical studies for SCI therapy are summarized. Finally, we discuss current limitations, translational challenges, and future perspectives in the field. This review aims to serve as a reference for the future development of functional biomaterials to further improve spinal cord regeneration.